Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

The latest research findings on bidirectional regulation of neuro-immunity through traditional neural circuits shed new light on the theoretical basis of the role of vidian neurectomy (VN). This article aims to provide a comprehensive understanding of VN, including the history of VN, the principle of neuroimmuno-interaction, the applied anatomy of VN as well as the methods of transnasal endoscopic surgery. Additionally, we introduce the concept of the nose-brain axis, which was proposed based on the advancement in the area of neuro-immune interactions.

Aim To investigate the relationship between fibrinogen(FIB)and the progression of coronary plaque stenosis rate in patients with type 2 diabetes mellitus(T2DM).Methods Hospitalized T2DM patients who underwent two or more coronary CT angiography(CCTA)examinations in the First Affiliated Hospital of Xi'an Jiaotong U-niversity from January 2015 to December 2020 were included.The subjects were divided into high FIB and low FIB groups according to the median of FIB.The differences in the progression of coronary plaque stenosis rate and other clini-cal characteristics were compared between the two groups,and the relationship between FIB level and the progression of coronary plaque stenosis rate was analyzed by Spearman's correlation analysis and Logistic regression.Results A total of 145 patients were included,73 in the high FIB group and 72 in the low FIB group at baseline,with a median follow-up time of 25(18,40)months between CCTA.The age,proportion of women,and the progression of coronary plaque ste-nosis rate were higher in the high FIB group than those in the low FIB group,and the differences were statistically signifi-cant(P＜0.05).FIB level was positively correlated with the change in coronary plaque stenosis rate(r2=0.308,P＜0.001).Multivariate Logistic regression analysis showed that FIB level was a risk factor for the progression of coronary plaque stenosis rate in patients with T2DM(OR=5.25,95％CI:1.97～14.02,P＜0.001),after adjusting for age,sex and other clinical risk factors.Conclusion High baseline FIB level is an independent risk factor for the progression of coronary plaque stenosis rate in patients with T2DM,and monitoring FIB level is beneficial to cardiovascular risk stratifica-tion in patients with T2DM.

[This corrects the article DOI: 10.1016/j.apsb.2024.04.021.].

Objective : To study the effect of EFHD2 protein deletion in Sertoli cells on Occludin，a component of tight junction protein and the localization and expression of EF-hand domain family member D2 (EFHD2) in mouse testis． Methods : Total RNA and protein were extracted from adult mice's heart ，liver ，spleen ，lung ，kidney， brain and testis tissues．The mRNA and protein levels of EFHD2 in each organ tissue were detected by qRT-PCR and Western blot．Immunofluorescence and immunohistochemistry detected the localization and expression of EF- HD2 in testicular tissues．SiRNA interference was used to reduce EFHD2 in Sertoli cells to detect Occludin protein expression. Results : qRT-PCR showed that the expression of EFHD2 was the highest in the testis．Western blot results showed that the expression level increased in testis tissue．Indirect immunofluorescence and immunohisto- chemistry results showed that the protein was mainly distributed in Sertoli cells and co-localized with cytoskeletal Vimentin，indicating that the protein was expressed in Sertoli cells．After the decrease of EFHD2 protein expres- sion，Occludin protein expression also decreased． Conclusion The expression of EFHD2 protein in the testis is relatively high，mainly distributed in Sertoli cells of the testis，co-localized with Vimentin，and can affect the nor- mal expression of tight junction protein Occludin．It is suggested that EFHD2 can promote and maintain the junction structure of Sertoli cells and provide a stable microenvironment for spermatogenesis.

Objective To analyze the effects of rapid rehabilitation surgical procedures on recovery and stress response in patients undergoing hepatectomy.Methods Retrospective analysis of 60 patients with liver resection in Zhujiang Hospital of Southern Medical University from January 2012 to December 2015,40 males and 20 females.According to the rehabilitation method,it was divided into intervention group (n=30) and control group (n=30).The operation time,intraoperative blood loss,postoperative complications,and interleukin-6 (IL-6),C-reactive protein (CRP),and white blood cell count (WBC) on days 1st,3rd,and 5 th before and after surgery were compared between the two groups.Results Both groups completed the operation successfully.There was no significant difference in intraoperative blood loss and operation time between the two groups (P＞0.05).The duration of postoperative ventilation and postoperative hospitalization in the intervention group was less than that in the control group,and the incidence of postoperative complications (23.3％ vs.50.0％) and the first and second day after surgery were lower than those in the control group,with statistically significant differences (P＜0.05).On the first,third and fifth days after surgery,IL-6 and CRP in the intervention group were lower than those in the control group,respectively (64.96± 24.10) μg/L vs.(286.74±67.98) μg/L,(60.52±18.31)μg/L vs.(162.33±52.62) μg/L,(31.61± 9.42) μg/L vs.(77.44±24.54)μg/L and (24.64±17.45) mg/L vs.(41.46±20.79) mg/L,(81.11± 36.58) mg/L vs.(117.23±44.80) mg/L,(44.90±22.31) mg/L vs.(65.27±38.05) mg/L,the differences were statistically significant (P＜0.05).Conclusion The concept of rapid rehabilitation surgery applied to patients with hepatectomy can reduce postoperative stress response,reduce postoperative complications,and accelerate the recovery process.

Objective: To compare the biomechanical performance between the single- versus double-threaded cannulated screws in the treatment of femoral neck fractures of Pauwels type Ⅲ. Methods: Models of femoral neck fracture of Pauwels type Ⅲ (70°) were made of the Sawbone synthetic composite femurs. All specimens were divided into 2 groups (n=12). Group A was fixated with single-threaded cannulated screws and group B with double-threaded cannulated screws, both in an inverted triangle configuration. The screws ranged from 90 to 95 mm in length and from 7.3 to 7.5 mm in diameter. All the specimens were subjected to axial stiffness and failure load tests with 7° valgus (simulating normal two-legged weight-bearing stance) and 25° valgus (simulating normal one-legged weight-bearing stance) and torsion test as well. The 2 groups were compared in the torques at axial stiffness angles of 1°, 2°, 3°, 5° and 7°. Results: Group B had significantly greater axial stiffness at 7° valgus and 25° valgus (89±26 N/mm and 128±37 N/mm) and failure load (1,154±368 N) than group A did (36±12 N/mm and 47±16 N/mm; 688±94 N) (P< 0.05). The torques increased with the increase in rotation angle in both groups. However, the torques in group B (3.26±0.96, 4.16±1.23, 4.64±1.13, 5.59±1.26 and 6.53±1.47 N·m) were all significantly larger than in group A (1.44±0.19, 2.03±0.41, 2.33±0.62, 2.74±0.87 and 3.05±1.07 N·m) (P<0.05). Conclusion Double-threaded cannulated screws may provide better biomechanical stability than single-threaded ones, due to their substantial improvement in anti-compression and anti-rotation performance.

Objective To study the correlation between the clinical characteristics of HCC patients with different phenotype circulating tumor cells in the peripheral blood.Methods 77 patients with HCC and 21 patients with benign liver diseases treated at Zhujiang Hospital of Southern Medical University from April 2015 to December 2016 were retrospectively studied.The CanPatrolTM System was adoptedto detect epithelial-mesenchymal phenotype CTCs in the peripheral blood.This study aimed to clarify whether the epithelial-mesenchymal phenotype CTCs were specifically originated from the tumorand to investigate the correlation between CTCs and the clinical features of the patients.Results Using epithelial and mesenchymal markers,the CTCs were divided into three subtypes:epithelial,mesenchymal and mixed CTCs.No epithelial-mesenchymal phenotype CTCs were detected in patients with benign liver diseases.The positivity rates of epithelial,mixed and mesenchymal CTCs in the peripheral blood of 77 patients with HCC were 37.7％ (29/77),74.0％ (57/77) and 50.6％ (39/77),respectively.The positivity rates of epithelial-mesenchymal phenotype CTCs in patients with HCC were significantly higher than the group of patients with benign liver diseases (P ＜ 0.05).The positivity rates of epithelial CTCs were significantly correlated with AFP,number of tumor and portal vein tumor thrombus (P ＜ 0.05).The positivity rates of mixed CTCs were significantly correlated with portal vein tumor thrombus,tumor differentiation and BCLC stage (P ＜ 0.05).The positivity rates of mesenchymal CTCs were significantly correlated with tumor size,portal vein tumor thrombus,tumor differentiation and BCLC stage (P ＜ 0.05).Conclusions The positivity rates of epithelial,mixed and mesenchymal CTCs were closely related to different aspects of clinical characteristics of patients with HCC.These CTCs may serve as indicatorsto evaluatethe progress of HCC.

OBJECTIVETo investigate the effect of galectin-3 in inducing the differentiation of rat bone marrow mesenchymal stem cells (BMSCs) into hepatocyte- like cells and explore the involvement of the signaling pathways in the induced cell differentiation.

METHODSThe third passage of cultured rat femoral BMSCs were treated with 0.5 μg/mL galectin-3, 20 ng/mL hepatocyte growth factor (HGF) or both to induce their differentiation, with untreated rat BMSCs and hepatocytes as controls. At 7, 14, 21 and 28 days of induction, the cells were examined for morphological changes followed by glycogen staining, quantitative real-time PCR and Western blotting. Gene microarray technique was used to examine the mRNA expression profile of the BMSCs induced with galectin-3. The BMSCs were also induced with galectin-3 in combination with XMU-MP-1, a Hippo signaling pathway inhibitor, after which Western blotting was performed to detect the expressions of YAP, P-YAP, ALB, AFP and CK-18 in the cells.

RESULTSThe cells isolated from the femoral bone marrow of SD rats showed a consistent surface marker phenotype with the BMSCs. Induction with galectin-3, HGF, or both all resulted in gradual morphological changes of the BMSCs into hepatocyte-like cells, and the cells with a combined induction for 28 days showed the highest morphological similarity with hepatocytes. The cells induced with galectin-3, HGF, or their combination for 28 days all showed increased positivity rate of glycogen staining, which was the highest in the cells with combined induction ( < 0.05) without significant difference between the cells induced with galectin-3 and HGF alone ( > 0.05). Induction with galectin-3 and HGF alone both increased the expressions of AFP, ALB and CK-18 mRNAs in the cells, and their expression levels were similar between the cells at 28 days ( > 0.05). Galectin-3 and HGF did not show an interactive effect on the mRNA expressions of AFP (=0.236, =0.640) or ALB (=50.639, =0.000), but had a synergistic effect on CK-18 mRNA expression (=50.639, =0.000). The protein expressions of AFP, ALB and CK18 were also increased in the induced cells but not detected in the cells without induction. Gene microarray results revealed 27 up-regulated genes and 62 down-regulated genes in galectin-3-induced BMSCs involving TGF-β, PI3K-Akt and Hippo signal pathways. Induction with galectin-3 and galectin-3+XMU-MP-1 increased YAP expression in the cells, and galectin-3+XMU-MP-1 was more efficient to induce the differentiation of the BMSCs.

CONCLUSIONSGalectin-3 can induce the differentiation of rat BMSCs into hepatocyte-like cells, and the combination with HGF increases the efficiency of induced differentiation of the cells. TGF-β, PI3K-Akt and Hippo pathways are involved in the induced differentiation of the BMSCs, and inhibiting Hippo pathway can improve the induction efficiency.

Objective To evaluate the value of fast track surgery (FTS) in laparoscopic hepatectomy.Methods The clinical data of 142 patients undergoing laparoscopic liver resection from January 2014 to January 2016 were analyzed retrospectively.74 patients received fast track surgery treatment (FTS group) and 68 patients received traditional treatment methods (control group).Results Compared with control group,FTS group had a shorter operative time and less blood lose (t =2.279,t =2.432,P ＜0.05),quicker postoperative intestinal function recovery (t =3.548,P ＜ 0.05),a shorter postoperative hospitalization time (t =2.821,P ＜ 0.05),a lower hospitalization cost (t =2.507,P ＜ 0.05),a lower postoperative VAS scores (t =3.394,t =3.176,t =7.079,P ＜ 0.05) in 3 post-op successive days.There were 3 patients with major post-op complications in FTS group (4.05％,3/74) compared with 4 cases in control group (5.88％,4/68) (x2 =0.253,P ＞ 0.05).Conclusion The application of fast track surgery in laparoscopic liver resection is safe and effective,and helpful in reducing patients' inhospital cost.